Head direction cells in rats with hippocampal or overlying neocortical lesions: evidence for impaired angular path integration

Abstract

Rodents use two distinct navigation strategies that are based on environmental cues (landmark navigation) or internal cues (path integration). Head direction (HD) cells are neurons that discharge when the animal points its head in a particular direction and are responsive to the same cues that support path integration and landmark navigation. Experiment 1 examined whether HD cells in rats with lesions to the hippocampus plus the overlying neocortex or to just the overlying neocortex could maintain a stable preferred firing direction when the rats locomoted from a familiar to a novel environment, a process thought to require path integration. HD cells from both lesion groups were unable to maintain a similar preferred direction between environments, with cells from hippocampal rats showing larger shifts than cells from rats sustaining only cortical damage. When the rats first explored the novel environment, the preferred directions of the cells drifted for up to 4 min before establishing a consistent firing orientation. The preferred direction was usually maintained during subsequent visits to the novel environment but not across longer time periods (days to weeks). Experiment 2 demonstrated that a novel landmark cue was able to establish control over HD cell preferred directions in rats from both lesion groups, showing that the impairment observed in experiment 1 cannot be attributed to an impairment in establishing cue control. Experiment 3 showed that the preferred direction drifted when HD cells in lesioned animals were recorded in the dark. It was also shown that the anticipatory property of anterodorsal thalamic nucleus HD cells was still present in lesioned animals; thus, this property cannot be attributed to an intact hippocampus. These findings suggest that the hippocampus and the overlying neocortex are involved in path integration mechanisms, which enable an animal to maintain an accurate representation of its directional heading when exploring a novel environment.

Fig. 1.

Overhead view of the dual-chamber apparatus. The novel portion of the apparatus includes the adjoining passageway and rectangular arena. Note that the cue card in the novel section of the apparatus is displaced 90° from the position of the card inside the cylinder.

Fig. 2.

Diagrammatic sequence for the procedure used in experiment 2. The overhead views of the cylindrical arena are shown during the four phases of the experiment. The surrounding environment for the no-cue session is identical to what the animal experienced during the daily screening sessions. After introduction of the white card during the insert-cue session, the animal is removed from the cylinder and returned to its home cage for at least 4 hr (Delay Period). The card is then rotated ±90°, and the animal is returned to the cylinder (Rotate Cue). Shortly afterward, a return-cue session is conducted in which the cue card is returned to the position it occupied in the insert-cue session. The floor paper was changed between all sessions after the insert-cue session to remove lingering olfactory cues. The designation of angular headings for experiments 1 and 2 are shown in the top right corner.

Fig. 3.

Schematic coronal sections comparing the largest and smallest lesions in the HPC group with a rat brain atlas (Paxinos and Watson, 1986). Each row illustrates a control and HPC section (left and right, respectively) at a particular distance relative to bregma (shown at thefar right). All shaded areas in the smallest lesion were also damaged by the largest lesion.DG, Dentate gyrus; FF, fimbria–fornix;FR, frontal area 1 and 2; HPC, hippocampus; HL, hindlimb area; LD, laterodorsal thalamic nucleus; LV, lateral ventricle;Oc1m, occipital 1 (medial); Oc2l,occipital 2, (lateral); Oc2m, occipital 2 (medial);Par 1, parietal 1; RS, retrosplenial cortex; Sub, subiculum.

Fig. 4.

Schematic coronal sections showing cortical lesions from the CTX group. Examples from the two animals having the smallest and largest lesions are shown. The distance of each section from bregma is indicated at the far right. See Figure 3legend for classification of brain areas.

Fig. 5.

A, Firing rate versus HD plots for an HD cell from a hippocampal animal in the familiar and novel environments. This cell shifted its preferred direction 102° between the familiar (cylinder) and novel (rectangle–passageway) sections of the dual-chamber apparatus. The novel plot illustrates the firing activity of the cell after the initial 3 min of the rat’s first visit to the novel section. B, Group data showing the mean absolute values of directional shift between the familiar and novel sections for the three groups. Asterisks indicate levels of significance relative to controls (*p < 0.05; **p < 0.01). There was also a significant difference between the CTX and HPC groups (†p < 0.01).

Fig. 6.

Polar plots showing the angular shifts in preferred direction during the first visit to the novel environment (novel session). Each dot on the periphery represents the magnitude of shift in the preferred direction for one HD cell. Each HD cell was recorded from a different animal. In general, HD cells in the control group maintained their preferred direction between the familiar and novel sections, with a small CW shift bias.Squares indicate the preferred direction shifts from the four control animals that were run in the present set of experiments. The CTX group had larger shifts than the controls, and these shifts were clustered around 0°. The HPC group had larger directional shifts than both the control and CTX groups, and the directional shifts were distributed randomly. The two open circles in the HPC group denote cells that drifted >180° in the CW direction.

Fig. 7.

Drift in the preferred direction of a cell during the first exposure to the novel environment. The preferred direction of this cell was ∼40° in the familiar cylinder. When the animal entered the novel section, the preferred direction drifted in a CW direction during the first few minutes. After ∼3 min, the cell adopted, and subsequently maintained, a preferred direction of ∼205°. The reduced mean firing rates during the 1 min time periods are probably an artifact caused by averaging the changing preferred firing direction. The thick line from the 3–4 min epoch indicates the firing orientation that was eventually established and maintained across repeated visits to the novel environment.

Fig. 8.

Individual 1 min samples of directional shift across different HD cells in the HPC group. The shift in preferred direction for each 1 min time period was compared with the baseline measure when the animal was located inside the cylinder just before entering the rectangle–passageway. The graph indicates that the preferred directions (1) shifted during the first minute of exposure to the novel environment, (2) frequently continued to drift over the next 2 min, and (3) were relatively stable after ∼3 min.

Fig. 9.

Frequency histogram categorizing the animal’s repeated visits to the familiar and novel sections.Environment indicates which part of the apparatus the animal was in for a given visit (familiar or novel).Characteristic PFD (preferred firing direction) indicates the typical preferred direction the cell adopted for an individual visit to one of the environments. The four pairs ofbars on the left represent all occasions when the preferred direction of a cell was within ±18° of its preferred direction in the animal’s first visit to that chamber. A cutoff value of 18° was chosen because it was at the upper range of values normally observed between sessions. A cell was consideredConsistent if its preferred direction was within ±18° of the direction established during the rat’s first visit to a given section (Familiar/Familiar orNovel/Novel). Inconsistent visits occurred when the preferred direction of a cell did not change after the animal crossed between sections, resulting in the cell firing within ±18° of the preferred direction typical of the other section of the dual-chamber apparatus (Familiar/Novel orNovel/Familiar). Other includes those visits in which the cell failed to fire within ±18° of its typical preferred direction in either section of the apparatus. In the vast majority of visits, the preferred direction of the cell appropriately matched the environment the animal currently occupied (Consistent). Occasionally, the firing of the cell was discordant with the environment (Inconsistent orOther). In seven of eight instances, the preferred direction characteristic of the rectangle–passageway was maintained when the animal returned to the cylinder.

Fig. 10.

Consistency of the newly established preferred direction in the novel environment. The histogram shows the frequency in the magnitude the preferred direction shifted between days 1 and 2 in the novel section. The numbers along the abscissa indicate the absolute value of the angular shift. Approximately half the animals (6/12) maintained the same preferred direction (±12°) in the novel environment over 24 hr. Many of the remaining animals exhibited large differences in preferred direction between the two days, indicating that the preferred direction established the previous day, although stable within the same recording session, was unstable over 24 hr.

Fig. 11.

Polar plots illustrating the shift in preferred directions for HD cells in the HPC and CTX groups during the 90° cue card rotation sessions. A value of 90° corresponds to an equivalent shift of the preferred direction of a cell, and a 0° shift indicates an absence of cue control by the white card. In both groups of animals, most HD cells exhibited a change in preferred direction that followed the angular rotation of the novel cue. This result occurred in the first set of cue-rotation sessions after the 4 hr delay (insert-cue vs rotate-cue) and when the cue card was returned to its initial position a few minutes later (rotate-cue vs return-cue sessions). These data indicate that the novel environmental cue was able to rapidly establish control over the preferred directions of HD cells in the lesioned animals.

Fig. 12.

HD cell responses in the dark recorded from a lesioned animal. The graph shows the running total drift in preferred direction over 20 min. In the sessions with the lights on, the preferred direction fluctuated around 0°. In contrast, in the dark session without the cue card, the preferred direction continuously drifted in the clockwise direction. The drift is not attributable to the absence of the cue card, because the drift during light sessions with and without the cue card was very small (see Experiment 3: dark sessions in Results). Hash marks between minutes 6 and 7 indicate the “wrap-around” point across 180°. The actual drift magnitude between minutes 6 and 7 was −18°.